DESCRIPTION: (Applicant's Abstract) High-throughput and automated DNA sequencing instrumentation that reduces the cost of sequencing is needed. Multiple-capillary electrophoresis has proven capable of meeting this need. This technology is now well established and has proven to be a significant advance over the previous slab gel technology. However, it is apparent that further development can lead to significantly increased reliability, lower instrument costs per sample, and increased sensitivity that would allow much smaller sequencing samples and concomitantly much lower sequencing costs. SpectruMedix Corporation's multiple-capillary technology uses "on-column" detection, which has several advantages over detection methods used in other capillary array sequencers. One advantage is that it allows simultaneous detection of 384 capillaries, so that upgrading the 96-capillary instrument to a 384-capillary instrument can be accomplished by merely upgrading the optical detection system including the CCD camera, the camera lens, and the laser, without any compromises in performance. These upgrades have been tested and verified to perform well. This 384-capillary instrument will dramatically increase capillary array electrophoresis throughput. Once the 384-capillary sequencer prototype is assembled, it will be sent to a sequencing production facility to optimize its compatibility leading to full integration and utilization. The major increase in throughput combined with further technology improvements to yield in excess of 1200 base read-length will allow dramatic cost reduction per sample and per sequenced base.